The global mission of the Developmental Resource for Biophysical Imaging and Opto-electronics is the design and development of new technologies for the visualization and measurement of biological processes with the ultimate aim of solving fundamental problems in biomedical research. This Resource concentrates on the direct optical observation of raw biological events. Physical techniques and instrumentation are optimized for sensitive investigations of single molecules or small groups of molecules within a dynamical system or living specimen. Fluctuation Correlation Spectroscopy (FCS), an analysis technique which distills dynamical information from the fluctuations in a fluorescence signal, enables measurement of molecular dynamics and intermolecular kinetics in extremely sparse solutions. Technological advances have enabled previously difficult dynamical measurements: protein folding, in vivo molecular dynamics, and single molecule analysis. The Optical Force Microscope (OFM), a Resource technology composed of a probe particle suspended by optical tweezers, makes possible measurements of delicate surfaces and tiny forces. The primary focus of this Resource has now become the development and application of its latest invention: multi-photon excitation (MPE) for microscopy, which enables 3-d localized excitation for imaging, photobleaching and photo-activation deep within thick tissue. MPE provides the ability to observe dynamical molecular processes in live tissues with subcellular detail, an experimental regime that has been largely unexplored. Other vital methods, such as ultrasound, NMR, PET, yield typical resolutions in the millimeter range. MPE accesses previously inaccessible spectral windows such as tissue and drug auto-fluorescence. These capabilities and some unexpected discoveries have recently drawn this Resource to focus on problems with direct biomedical relevancy. Collaborations have introduced direct disease relevance: Alzheimer's osteoporosis, liver degeneration, serotonin secretion, auditory neurobiology, stroke and malignancy.